Aza-indolizine with bridgehead nitrogen. Metalation, halogen-metal exchange and directed ortho-lithiation in the imidazo[1,2-a]pyrazine series

Abstract The n -BuLi and lithium 2,2,6,6-tetramethylpiperidine (LTMP) metalation of imidazo[1,2- a ]pyrazine heterocycles and subsequent quenching with electrophiles is described. Bromine atoms exhibit different behaviours towards lithiation depending on their positions (3 or 6) on the imidazo[1,2- a ]pyrazine heterocycle. Halogen-metal exchange occurs readily with the bromine on position 3. On the contrary, bromine on position 6 only leads to C-5 substituted derivatives further to an ortho -directing effect.